Biomedical subjects
Publications and source records attributed to H Hoffmann.
Chronicity in serious mental disorders emanates from deficient ecological resources interacting with vulnerable individuals. Rehabilitation can succeed if an integrated and individualized approach is augmented by appropriate ecological supports.
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Between May 1985 and September 1990, 291 ureteroscopies were performed either for primary or secondary stone therapy or for diagnostic purposes. Rigid ureteroscopes (12.5 or 9.5 French) were used without dilation of the ureteral orifice. 83% of the stones could be removed either by direct extraction or electrohydraulic or ultrasound lithotripsy. The highest failure rates (25.6%) occurred in stones located in the upper ureter, the lowest failure rate (9.6%) resulted from treatment of lower ureteral stones. 3.4% complications were observed such as perforation, leakage, stenosis and septicemia. After an average follow-up of 4.5 months, 1 in 70 patients revealed an ureteropelvic stricture which was treated with open surgery. The ureterorenoscopy represents an effective and low-risk primary and secondary method for treatment of ureteral stones in stone centers using extracorporeal lithotriptors which are exclusively equipped with ultrasound detection devices.
Traditional explanatory models, based on core psychological deficits, vulnerability-stress models or distinctions between negative and positive symptoms, may not be sufficient to understand the phenomenon of chronicity. This linear thinking, looking for monocausal explanations, should be replaced by exploring multicausal and circular processes over time, including the individual ecological context of a given patient. Thus, chronicity appears to result much more from endless loops and irreversible bifurcations in its dynamics over time than to be a stable state. Furthermore, the current views on psychopathology and prognosis need to be fundamentally reexamined in the light of this new way of thinking. For understanding and treatment of chronic psychoses, this ecological perspective implies programs which do not focus only on the patient, but look for 'ecological niches' and interventions favoring synergetics and self-organization within the social networks and at the worksite of a given patient. A recently implemented five-step program for vocational rehabilitation and the corresponding research plan will be presented and discussed.
Endotoxin shock and contact system activation were used to study effects of hirudin, antithrombin III, eglin C, aprotinin, and [Arg15]-aprotinin in anesthetized pigs. Alterations in the systemic and pulmonary circulation were in part prevented by administration of the inhibitors.
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We wanted to demonstrate that the neutrophil elastase inhibitor eglin C reduces the loss of intravascular protein in endotoxin (LPS) shock and that effective concentrations are present in lymph. We used 45 anesthetized miniature pigs in a randomized, controlled trial. LPS 10 micrograms/kg/hr was given for 6 hr. Recombinant eglin C was given before LPS (250 nmol/kg) and continuously at 250 nmol/kg/hr (n = 18); septic controls received saline (n = 18); nine nonseptic controls were used. Eglin C significantly reduced the loss of intravascular protein (plasma volume times plasma protein concentration) from -0.79 g/kg in septic controls to 0.42 g/kg in eglin C-treated animals and reduced plasma concentration of neutrophil elastase, bound to the leukocyte neutral protease inhibitor (LNPI), but systemic hypotension was unchanged. Six additional pigs were anesthetized, prepared with a thoracic lymph fistula, and received eglin C at 475 nmol/kg/hr; three received saline; three received LPS. Eglin C concentrations in lymph were comparable to those in plasma. We conclude that eglin C reduced the loss of intravascular protein during LPS shock and attained effective concentrations in lymph.
Out of the group of 2-amino-oxazoles 1 was found to be the most potent antiviral compound. Following p.o. or s.c. administration to rats, the 14C-labeled 1 was quickly and completely absorbed. The TRA was eliminated mainly via the kidneys and the liver with half-lives between 32 and 42 h. The acute pharmacodynamic effects of 1 were decrease of blood pressure, bradycardia, and inhibition of both gastric emptying and acid secretion. On smooth muscles spasmolytic and alpha-anti-adrenergic actions were predominant. After single administration the following MTD's were determined: 30 (mouse), 20 (rat), 10 mg/kg i.v. (pig), and 500 (mouse, rat), greater than 100 mg/kg p.o. (pig), respectively. In a subchronic toxicity study in rats, oral doses of 1 between 15 and 240 mg/kg given daily for 4 weeks were tolerated without any severe alterations related to the drug.
It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the alkylating antineoplastic agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia-related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals.
Notwithstanding considerable success, the concepts currently applied by vocational rehabilitation workshops for persons with chronic mental illness are deemed open to criticism in some respects. Presented is the PASS programme, developed on the basis of more than two decades of experience with the clinic's own rehabilitation workshop. The greater part of the five-phase programme no longer occurs within the workshop but is spent at training workplaces with regional firms. A mobile rehabilitation team does not only support the patients at their training facilities but also their colleagues and immediate superiors, who have been prepared for their forthcoming tasks by psychoeducational information meetings. These community-based, ecological system-related aspects of the programme are complemented by repetitive social skills training and group work with relatives. Assessments carried out in each phase provide important decision-making data for programme development and render its scientific evaluation possible. Our experience so far demonstrates the possibility of recruiting enterprises to provide training places.
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Inhibition of activated clotting factors is an important therapeutic approach in disseminated intravascular coagulation (DIC). We examined the possible protective effect of a purified complex of human antithrombin III (AT III) and heparin in endotoxin-induced DIC in pigs. Two groups of endotoxemic pigs were studied. AT III-heparin group pigs (n = 8) were pretreated with a bolus injection of 500 units AT III-heparin complex, followed by a continuous infusion of 1000 units of the complex for 6 hours given simultaneously with the infusion of 10 micrograms/kgh of S. abortus equi endotoxin. Controls (n = 9) were given saline in addition to the continuous infusion of endotoxin. AT III activity, prothrombin and soluble fibrin in plasma were determined by chromogenic substrate methods. Fibrinogen was measured turbidimetrically. Human AT III antigen in the treated group was 64 +/- 3% at 2 hours and increased to 84 +/- 4% until the end of the experiment. AT III activity in the AT III-heparin group was elevated throughout the whole observation period (greater than 100%), whereas it was significantly lower in the controls. Prothrombin decreased similarly in both groups by approximately 35% until the end of the experiment. AT III-heparin treatment significantly attenuated the endotoxin-induced consumption of fibrinogen and completely prevented the increase in soluble fibrin in plasma. However, no significant effect of AT III-heparin was observed on endotoxin-induced mortality and dysfunction in pulmonary gas exchange. Therefore we conclude that the purified AT III-heparin complex inhibits thrombin effects and prevents development of DIC, but fails to significantly influence clinical outcome in endotoxin shock of the pig.
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Interactions between olfactory and brightness conditioning were examined in infant (16-day-old) and adult rats. Conditioning to an odor (methyl salicylate [MS] paired with footshock [FS]) was followed by subthreshold conditioning to an unscented black box (paired with FS). Controls were given unpaired presentations in either the 1st or the 2nd phase of this treatment. No age-related differences in conditioning occurred when either phase was presented alone. Significant aversion to the black box was observed after the experimental treatment only in infants, and brightness conditioning potentiated odor conditioning in infants but not adults. In the infants, odor-extinction procedures weakened the aversion to the black box as well as to MS. Olfactory-to-visual transfer required that the same unconditioned stimulus be paired with both conditioned stimuli. These results may reflect an infantile disposition for unitization.
The AEDV in the umbilical artery or the foetal aorta is considered to be the most severe waveform abnormality. Using pulsed Doppler, we found such a waveform in 51 foetuses out of 954 high-risk pregnancies (33/51 in both vessels, 17/51 aorta only and 1/51 umbilical artery only). A reverse flow was registered in 24 foetuses. The outcome was compared with that of a control group (n = 72) showing normal Doppler findings. The following parameters were highly significant (p less than 0.001): Rate of Caesarean section owing to foetal distress (85.3% to 4.8%), of growth retardation (IUGR) (66.7% to 6.0%), of premature delivery (73.5% to 7.5%), of low postnatal pH- and Apgar score (73.5 to 12.1%), of admission to the neonatal intensive care unit (94.1% to 8.6%), of morbidity (35.3% to 2.3%) and of mortality (41.1% to 0%). We observed 17/51 intrauterine and 4/51 postnatal deaths. The rate of malformations was 35.3% with 4 cases of aneuploidy. Considering the malformations, the rate of corrected mortality was 23%. We found, that the association of an AEDV and the absence of severe IUGR is highly suspicious of malformation. We also observed, that congenital heart diseases (CHD) could lead to an AEDV too. An AEDV precedes a pathological cardiotocogram (CTG) with a latency of 0 to 35 days (mean 9.5 days). This latency is not predictable, but we think, that a reliable assessment of jeopardy is possible by analysing further vessels (Aa. arcuatae, A. renalis, A. carotis interna): 72.5% of the foetuses with AEDV had high indices in the carotid artery and 93.1% among these showed a pathological CTG pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate short-term activation and inhibition of fibrinolysis during shock, we studied plasma levels of tissue-type plasminogen activator (t-PA) and t-PA inhibition capacity (PAI) in anaesthetized pigs. t-PA in euglobulin fractions of plasma was measured by the conversion of plasminogen to plasmin in the presence of fibrin split products. Plasmin thus generated was measured in a chromogenic substrate assay. PAI was measured as plasma inhibition capacity for human melanoma t-PA. Controls (n = 8) had constant t-PA and PAI for 6 h. Lipopolysaccharide from Salmonella abortus equi in four different doses (n = 9 - 11), or live Escherichia coli (n = 3) induced a transient t-PA increase with peak values at 2 h. PAI decreased to 50% at 2 h and increased to 250% at 6 h. Phorbol myristate acetate (n = 7) induced no change of t-PA or PAI. Dextran sulphate (n = 4) produced a t-PA rise at 30 min, followed by a rapid decline. Endotoxin was an appropriate stimulus for activation and inhibition of fibrinolysis whereas phorbol ester failed to elicit this response.
Pentoxifylline (PTX), a methylxanthine, can suppress polymorphonuclear leukocyte (PMN) activation and attenuate sepsis-induced acute lung injury. We investigated whether PTX prevents non-PMN-dependent lung injury. First we studied four groups of granulocyte-depleted guinea pigs (control, PTX, Escherichia coli, and E. coli + PTX). Lung injury was assessed by wet-to-dry lung weight (W/D) ratio and lung tissue-to-plasma 125I-albumin ratio (albumin index, AI). The E. coli group showed a significant increase in the lung W/D ratio and AI compared with the control and PTX groups. However, PTX did not prevent the E. coli-induced increase in the lung W/D ratio and AI. Next we investigated the effects of PTX on endothelial cell monolayer permeability and adenosine 3',5'-cyclic monophosphate (cAMP) levels. Whereas E. coli lipopolysaccharide (LPS) alone increased the endothelial permeability, PMNs added to the endothelial monolayers and exposed to LPS enhanced the increase. PTX attenuated the permeability increase mediated by LPS-exposed PMNs. PTX did not prevent the LPS-induced increase in permeability when PMNs were not present, although PTX increased endothelial cell cAMP levels. These data demonstrate that 1) PTX does not prevent lung injury in granulocyte-depleted guinea pigs; 2) PTX does not prevent LPS-induced increases in endothelial cell permeability, despite increased cAMP levels; and 3) PTX attenuates PMN-dependent increases in endothelial cell permeability.